Background: Tacrolimus (TCR), also known as FK-506, is a biopharmaceutics classification system (BCS) class II drug that is insoluble in water because of its high log P values. After dermal application, TCR remains in the stratum corneum and passes through the skin layers with difficulty. Purpose: The objectives of this study were to develop and evaluate solid lipid nanoparticles (SLNs) with thermosensitive properties to improve penetration and retention. Methods: We prepared TCR-loaded thermosensitive solid lipid nanoparticles (TCR-SLNs) with different types of surfactants on the shell of the particle, which conferred the advantages of enhancing skin permeation and distribution. We also characterized them from a physic point of view and performed in vitro and in vivo evaluations. Results: The TCR contained in the prepared TCR-SLN was in an amorphous state and entrapped in the particles with a high loading efficiency. The assessment of ex vivo skin penetration using excised rat dorsal skin showed that the TCR-SLNs penetrated to a deeper layer than the reference product (0.1% Protopic^®). In addition, the in vivo skin penetration test demonstrated that TCR-SLNs delivered more drug into deeper skin layers than the reference product. FT-IR images also confirmed drug distribution of TCR-SLNs into deeper layers of the skin. Conclusion: These results revealed the potential application of thermosensitive SLNs for the delivery of difficult-to-permeate, poorly water-soluble drugs into deep skin layers.

Dual-drug delivery systems using hydrogel–nanoparticle composites have emerged as a versatile platform for achieving controlled, targeted, and efficient delivery of two distinct therapeutic agents. This approach combines the high loading capacity and tunable release properties of hydrogels with the enhanced stability and targeting ability of nanoparticles, providing synergistic benefits in various biomedical applications. While significant progress has been made, previous research has primarily focused on single-drug systems or simple co-delivery strategies, often lacking precise spatial and temporal control. This gap underscores the need for more sophisticated composite designs that enable programmable, multi-phase release. This review discusses representative fabrication methods, including physical embedding, covalent integration, and layer-by-layer assembly, to offer insights into practical implementation strategies. Also we present recent studies focusing on key applications—including wound healing, cancer therapy, infection prevention, transplant immunosuppression, and tissue regeneration—with an emphasis on composite design and formulation strategies, types of hydrogels and nanoparticles, and mechanisms of dual-drug release and evaluation. Recent advances in nanoparticle engineering and hydrogel formulation have enabled precise control over drug release and improved therapeutic outcomes. Dual-drug delivery systems using hydrogel–nanoparticle composites present a promising approach for overcoming the limitations of conventional monotherapy and achieving synergistic therapeutic effects. Ongoing research continues to optimize the design, efficacy, and safety of these systems, paving the way for their clinical translation.

Park CS, et al. Immune Netw. 2022 Feb;22(1):e13. https://doi.org/10.4110/in.2022.22.e13

Purpose: Dexamethasone (Dex) has long been used as a potent immunosuppressive agent in the treatment of inflammatory and autoimmune diseases, despite serious side effects. In the present study, Dex and model antigen ovalbumin (OVA) were encapsulated with poly(lactic-co-glycolic acid) to deliver Dex and OVA preferentially to phagocytic cells, reducing systemic side effects of Dex. The OVA-specific immune tolerance-inducing activity of the nanoparticles (NPs) was examined. Methods: Polymeric NPs containing OVA and Dex (NP[OVA+Dex]) were prepared by the water-in-oil-in-water double emulsion solvent evaporation method. The effects of NP[OVA+Dex] on the maturation and function of immature dendritic cells (DCs) were examined in vitro. Furthermore, the OVA-specific immune tolerizing effects of NP[OVA+Dex] were confirmed in mice that were intravenously injected or orally fed with the NPs. Results: Immature DCs treated in vitro with NP[OVA+Dex] did not mature into immunogenic DCs but instead were converted into tolerogenic DCs. Furthermore, profoundly suppressed generation of OVA-specific cytotoxic T cells and production of OVA-specific IgG were observed in mice injected with NP[OVA+Dex], whereas regulatory T cells were concomitantly increased. Feeding of mice with NP[OVA+Dex] also induced OVA-specific immune tolerance. Conclusion: The present study demonstrates that oral feeding as well as intravenous injection of poly(lactic-co-glycolic acid) NPs encapsulating both antigen and Dex is a useful means of inducing antigen-specific immune tolerance, which is crucial for the treatment of autoimmune diseases.